Abstract: As part of an ongoing project to explore filamentous fungi for anticancer and antibiotic leads, 11 compounds were isolated and identified from an organic extract of the fungus Scytalidium album (MSX51631) using bioactivity-directed fractionation against human cancer cell lines. Of these, eight compounds were a series of sorbicillinoid analogs (1–8), of which four were new (scalbucillin A (2), scalbucillin B (3), scalbucillin C (6) and scalbucillin D (8)), two were phthalides (9–10) and one was naphthalenone (11). Compounds (1–11) were tested in the MDA-MB-435 (melanoma) and SW-620 (colon) cancer cell lines. Compound 1 was the most potent with IC50 values of 1.5 and 0.5?µM, followed by compound 5 with IC50 values of 2.3 and 2.5?µM at 72?h. Compound 1 showed a 48-h IC50 value of 3.1?µM when tested against the lymphocytic leukemia cell line OSU-CLL, while the nearly identical compound 5 had almost no activity in this assay. Compounds 1 and 5showed selective and equipotent activity against Aspergillus niger with minimum IC values of 0.05 and 0.04?µg?ml-1 (0.20 and 0.16?µM), respectively. The in vitro hemolytic activity against sheep erythrocytes of compounds 1 and 5 was investigated and were found to provoke 10% hemolysis at 52.5 and 45.0?µg?ml-1, respectively, indicative of a promising safety factor.